Sex Differences in Taxane Toxicities

SIMPLE SUMMARY: Clinically observed sex differences in acute and long-term taxane chemotherapy-induced normal tissue toxicity are routinely documented but remain poorly understood despite the significant impact such toxicities have on treatment tolerance and quality of life outcomes in cancer survivors. This review draws from pre-clinical and clinical literature to highlight sex-specific mechanisms of action in taxane drug toxicity and proposes hypotheses for sex-specific clinical discrepancies in taxane-induced acute and long-term toxicities. To our knowledge, this is the first review exploring how sex as a biological variable impacts taxane-mediated mechanisms of action and clinical outcomes. In doing so, we have provided a novel framework to investigate and understand common sex differences observed in clinical and pre-clinical research. ABSTRACT: The taxane family of microtubule poisons and chemotherapeutics have been studied for over 50 years and are among the most frequently used antineoplastic agents today. Still, limited research exists characterizing taxane-induced sex-specific mechanisms of action and toxicities in cancer and non-cancerous tissue. Such research is important to advance cancer treatment outcomes as well as to address clinically observed sex-differences in short- and long-term taxane-induced toxicities that have disproportionate effects on female and male cancer patients. To gain more insight into these underlying differences between the sexes, the following review draws from pre-clinical and clinical paclitaxel and taxane oncology literature, examines sex-discrepancies, and highlights uncharacterized sex-dependent mechanisms of action and clinical outcomes. To our knowledge, this is the first literature review to provide a current overview of the basic and clinical sex dimorphisms of taxane-induced effects. Most importantly, we hope to provide a starting point for improving and advancing sex-specific personalized chemotherapy and cancer treatment strategies as well as to present a novel approach to review sex as a biological variable in basic and clinical biology.